A central role for serum lipids in the pathogenesis of vascular disease has long been postulated, but has remained an elusive problem for both the biochemist and the clinician. Since 1955, it has been known that prebeta lipoproteinemia is an early finding in ischemic heart disease and a constant finding in maturity-onset diabetes where vascular disease is a familiar part of the pathological process. The present investigation has posed two linking hypotheses from the last 6 1/2 years of investigation into the metabolism of this lipoprotein and its relationship to carbohydrate physiology: 1) Abnormalities of metabolism of the protein moiety associated with the circulating lipoprotein may be central to the pathophysiology of prebeta lipemia. 2) An hormonal basis for the lipemia with a relative excess of insulin and/or deficiency of glucagon "activity" may represent the initiating factors which alter carrier protein metabolism. If this sequence of events represents the mechanism and pathophysiology of some forms of human lipoprotein disease, then the implications in terms of diagnosis and therapy are clear. Finally, the elucidation of lipoprotein-carbohydrate-hormone interrelationships should importantly add to the present state of knowledge concerning intermediary metabolism. BIBLIOGRAPHIC REFERENCES: Eaton, R. Philip and D. S. Schade. 1977. Modulation of the Catabolic Activity of Glucagon by Endogenous Insulin Secretion in Obese Man, In Press. Acta Diabetologica Latina. Schade, D. S. and R. Philip Eaton. 1977. The Effect of Short-Term Physiological Elevations of Plasma Glucagon Concentration on Plasma Triglyceride Concentration in Normal and Diabetic Man. Horm. & Metab. Res., in press.